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Background: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a “public health emergency of international concern”. A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. Methods: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. Results: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. Conclusions: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

An infrequent thoracic and abdominal aortic aneurism occurred in a patient with a human immunodeficiency virus (HIV) infection well controlled by an effective combination antiretroviral therapy, already modified to minimize dysmetabolic abnormalities. No adjunctive risk factors for an accelerated atherogenesis were present (ie, cigarette smoking, arterial hypertension, metabolic syndrome, diabetes mellitus), the personal and family cardiovascular history were mute, and no infectious foci supported a mycotic aneurism. Moreover, alternative statin-fibrate therapy was administered since 18 months, and a diet-exercise program and a polyunsaturated fatty acids supplementation were recommended. Despite surgical positioning of an aortic endoprosthesis immediately after diagnosing the aortic aneurism, 11 months later an imminent aneurism rupture was avoided by the introduction of another endoprosthesis between the older thoracic graft and the suprarenal prosthetic device, although a revascularization of renal and mesenteric arteries became needed. The subsequent, 7-month-long follow-up did not disclose complications or sequelae, whereas HIV infection remained under control with a simplified, effective, and well-tolerated antiretroviral regimen. Unfortunately, a fatal relapse of ruptured aortic aneurism led rapidly our patient to death. Caregivers following HIV-infected patients should be aware of the increased risk of complicated, accelerated atherogenesis in these subjects, even when combination antiretroviral therapy is sufficiently well tolerated, and the great majority of known risk factors has been assessed and eventually treated. Severe gross vessel abnormalities deserve major attention and eventual specialistic surgery treatment, which may play an effective role in life-threatening conditions.

A rare case report of serious, relapsing, and difficult-to-treat Strongyloides stercoralisenteric infestation that occurred in a patient affected by the autoimmune Sjögren disease (a pathologic association never reported before), chronically treated with corticosteroids, has been presented and evaluated on the ground of the available literature evidences in this field. In particular, the role of underlying (and iatrogenic) immunodeficiency in the pathogenesis of S. stercoralispersisting infection and the unresolved diagnostic and therapeutic issues in the setting of strongyloidiasis are discussed. Particular attention is focused on the need to maintain clinical suspicion for this nematode worm infestation in patients suffering from a large spectrum of collagen vascular diseases, and the need for randomized clinical trials to determine suitable first-line and subsequent lines of treatment, especially when immunodeficiency and a relapsing Strongyloidesdisease are suspected.

Enfuvirtide (Fuzeon®, Roche), is the first member of a novel class of antiretroviral agents, the socalled fusion inhibitors, which act against HIV with a completely novel (extra cellular) mechanism of action, and can therefore be easily added to all anti-HIV association therapies including all other antiretroviral agents belonging to nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, since no interactions of any type are expected with enfuvirtide. Despite the need of a twice-daily parenteral (subcutaneous) delivery due to the polypeptide structure of the drug, and its proportionally short elimination lifetime, two extensive multicentre randomized clinical trials and a huge amount of other clinical and laboratory experiences confirmed the elevated potency and the safety profile of enfuvirtide in appropriate samples of HIV-infected patients (both adults and children), who failed and/or became intolerant to all previously available anti-HIV regimens, and had a very restricted choice of antiviral compounds showing residual activity. As a consequence, enfuvirtide is recommended as an adjunct to an "optimized background" containing at least one or two antiretroviral drugs, which are still active against the isolated viral strain, as assessed by resistance testing. The extremely promising profile of this novel anti-HIV drug and the reduced potential for the development of viral resistance (with no possibility of cross-resistance with the other anti-HIV classes) however warrant further pharmacokinetic, pharmacodynamic, pharmacogenomic, and pharmacoeconomic investigation. Also more extensive and prolonged clinical and quality of life studies are strongly needed to establish the best positioning of enfuvirtide in the current therapeutic guidelines of HIV disease and its future role, besides its current approval for salvage therapy of adult and pediatric HIV-infected patients with limited therapeutic options.

A case of nephrotic syndrome treated with associated cyclophosphamide and corticosteroids came to our attention after over 2 years of self-administered immunosuppressive therapy which remained unchanged and uncontrolled during this period. The self-administered therapy resulted in a severe cell-mediated immunodeficiency (as expressed by a nadir CD4lymphocyte count of 2 cellsμL). This led to a rapid unfavorable progression of hepatitis B, which was recently acquired and subsequently evolved into a severe cholestatic and fibrosing chronic hepatitis, causing multiple end-organ failure, and ultimately, death. This process was not reversed by lamivudine therapy, hemodialysis, and the use of a Molecular Adsorbent Recirculating System. The role played by repeated drug prescriptions from general practitioners without appropriate clinical and laboratory controls, and that of our patient's depression are discussed. Current literature related to the presented case and the ongoing debate regarding repeated prescriptions are considered in this study.

A reversal of key HIV protease mutations against tipranavir has been observed in a patient undergoing a late salvage antiretroviral therapy. Our patient initially introduced tipranavir/ritonavir in absence of an optimized background and novel drug classes, and nevertheless he experienced a virological-immunological benefit. Our report is a contribution to the present debate around the role of each single HIV protease mutation, and the validation of mutational “scores” (like the so-called tipranavir weighted score), to be applied to last-generation protease inhibitor compounds initially targeted on patients with limited, residual therapeutic options.

A HIV-infected patient treated since eight years with all antiretroviral classes save boosted protease inhibitors, at the time of changing therapy due to an emerging genotyping resistance to non-nucleoside reverse transcriptase inhibitors, experienced repeated episodes of hypersensitivity reactions to all available boosted protease inhibitors. After documenting a combined ritonavir and lopinavir hypersensitivity by means of a specific in vitro cellular antigen stimulation test (CAST), antiretroviral therapy was safely continued with unboosted atazanavir. According to our knowledge, we report the first case of application of the in vitro CAST assay to antiretroviral intolerance, and the subsequent, specific regimen selection in a HIV-infected subject who showed multiple allergy to all boosted protease inhibitors. Further, controlled investigation is strongly needed to implement in vitro allergometric testing in patients with HIV infection and related diseases, who are prone to show unpredictable drug intolerance reactions. In fact, HIV-infected patients may suffer from frequent allergic drug reactions which may be difficult to be systematically recognized (due to the frequent, multiple concurrent pharmacotherapy), while eventual drug rechallenges are expected to be potentially dangerous.

Aim of our report is to discuss some key adherence features in the real world, by reporting two exceptional patients, who deliberately took all antiretroviral medications at half-dosage compared with standard prescriptions, and maintained a fully stable and sustained virological and immunological response after 6-10 consecutive years. The potential causes and consequences of this apparent misconduct of our patients on drug tolerability, resistance development, compliance monitoring, direct drug delivery, and health care providers behavior, are discussed.